Description (provided by applicants): The objectives of this Core: Virology, are to support Research Projects and Cores by providing specific reagents, antiviral evaluations and in vitro and animal model efficacy data for CV-N, and formulations. This will be accomplished through reiterative analysis of CV-N preparations and combinations in a standard assessment algorithm (Objective 1). The screening algorithm has been designed specifically to allow the greatest flexibility in assessing the effect of purified CV-N proteins and formulations on cell-free and cell-to-cell transmission of HIV-1 and allowing incorporation of factors such as mucin, serum and red blood cells to assess CV- N action in a complex environment. The Core will also provide specific support by producing high quality virus stocks of subtype representative clinical isolates and multi-drug resistant viruses. The Core will also facilitate the transfer of antiviral screening technologies (Objective 2). Core C will perform experiments designed to develop CV-N resistant virus for reiterative testing of optimized lead CV-Ns (Objective 3). Expanded range of action and mechanism testing will be provided for lead CV- N proteins, formulations or combinations to meet the requirements of a preclinical virology assessment prior to advancement to clinical testing (Objective 4). Finally, CV-N formulations will be evaluated in a Rhesus macaque mucosal transmission model to: (1) determine the minimal effective concentration of CV-N; (2) determine the efficacy of a lead CV-N formulation; and (3) verify the lead formulation efficacy and/or determine the efficacy of a lead CV-N combination (Objective 5). These five objectives will facilitate the development of a lead CV-N topical microbicide by providing critical reagents and antiviral evaluations. Additionally, for lead materials this core will provide critical preclinical virology information needed to advance CV-N to initial clinical studies.